tarceva/rapamycin for children with low-grade gliomas with or without neurofibromatosis type 1 (nf1)

Conditions: Low-grade Gliomas

Summary: this study will evaluate the feasibility of combining two drugs, tarceva (an anti-egfr agent), and rapamycin (an mtor inhibitor), in children with progressive low-grade gliomas who have failed initial conventional treatment. in addition to evaluating the toxicity of this drug regimen, the potential efficacy of the regimen will be assessed.


Eligibility criteria:
inclusion criteria: * children less than 21 years of age, with or without neurofibromatosis, with recurrent low-grade gliomas. * patients with or without nf1 must have failed some form of conventional therapy, radiotherapy, or chemotherapy (carboplatin/vincristine) to be eligible, including those treated wtih initial surgery. patients do not have to have received radiotherapy to be eligible. * children with all types of histologically proven low-grade gliomas will be eligible; re-operation at the time of recurrence is not mandatory for entry on study. * patients with intrinsic brain lesions, believed neuroradiographically consistent with a low-grade glial tumor, with neurofibromatosis type 1 can be treated without histological confirmation. * patients without neurofibromatosis type 1 must have histological confirmation of a low-grade glial tumor prior to entry on study. * patients must have a karnofsky score of greater than or equal to 50% for children greater than 10 years of age, or a lansky score of greater than or equal to 50% for patients less than 10 years of age. * patients who are unable to walk because of paralysis, but who are able to use a wheelchair, will be considered ambulatory for purposes of assessing performance score. * patients must have a life expectancy of at least 12 weeks. * patients must be able to swallow medication in tablet form. * patients must have adequate organ function, including: peripheral anc of greater than 1,000/microliters; a platelet count of greater than 100,000/microliters; hemoglobin of greater than 8 gms,dl (prbc transfusions of allowed to maintain hemoglobin \> 8 g/dl) * patients must have adequate renal function, which is defined as a normal serum creatinine for age * patients must have adequate liver function, as defined as a total bilirubin or less than 1.5 times the upper limit of normal for age, and an sgpt (alt) of less than 2.5 times the upper limit of normal for age * patients must have had a mr scan within 3 weeks of starting treatment * all patients, and/or their parents or legal guardian, must sign a recent informed consent * all institutional, fda, and nci requirements for human study must be met. exclusion criteria: * patients must not have any other active tumors. * pregnancy or breast feeding is an exclusion criteria, as the potential mutagenicity and cytotoxicity of these drugs in developing fetuses are unknown. a pregnancy test must be obtained in females who are postmenarchal. males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * patients with uncontrolled infection are excluded. * patients who have previously received tarceva or rapamycin are excluded. * patients on antiepileptics and/or corticosteroids are allowed on study as long as they have been on a stable or weaning dose for 7 days prior to study initiation (defined as first day of treatment).